The world-wide need for donated blood is enormous. It was recently estimated that there is a world-wide shortage of donated blood in the area of 200 million units per year. While approximately 11 million units of blood are transfused in the United States each year, the number would be larger were it not for the concern about the transmission of infectious disease. Even with the extensive screening that is now performed on all donated blood, patients and their physicians still fear a repeat of the events of the 1980's, when many people were infected by HIV-contaminated blood. Approximately two-thirds of the donated blood in the U.S. is used during surgery, while the remainder is used in cases of emergency and for people with chronic anemia and other blood related ailments.
While the market remains essentially undeveloped in the U.S., a safe, effective and inexpensive blood substitute product could replace two-thirds of the transfusions, specifically in cases of surgery. Past research has demonstrated that the properties of surface-modified hemoglobin substitutes can be manipulated to provide improved blood flow to organs. See for example, U.S. Pat. No. 5,814,601, of Winslow, et al., which discloses a blood substitute with an oxygen-carrying component, the disclosure of which is incorporated herein by reference. However, in spite of the availability of blood substitutes, as yet, an inexpensive and reliable means for evaluating the properties of such blood substitutes has not been available.
Blood serves a duel function in the process of gas exchange within the body. It is responsible for the transport of oxygen to cells and tissue for aerobic metabolism. Secondly, blood functions to remove carbon dioxide, a by-product of aerobic metabolism, through the lungs. Failure to adequately perform these functions would result in eventual and inevitable cell death. In order for blood to successfully provide much-needed nutrients, as well as remove waste products from within the body, certain hemodynamic properties must be present. Fluid without the proper physicochemical properties will not function in the cardiovascular system.
Hemoglobin is the fundamental molecule for oxygen transport by blood. Hemoglobin is composed of four subunits, each subunit possessing an iron-containing heme group which is responsible for oxygen binding. With these four subunits, one hemoglobin molecule is capable of binding four oxygen molecules. Analysis of the hemoglobin-oxygen interaction is facilitated by plotting numerical blood saturation values against oxygen partial pressure, resulting in an oxygen equilibrium curve (OEC). The shape of the OEC is an important indicator of the ability of a blood sample to transport and deliver oxygen properly. Oxygen delivery needs to be precise. Early release will waste oxygen, and delivery of too much oxygen is believed to have detrimental effects on the vascular system including vasoconstriction and free radical production. In the design and evaluation of blood substitutes, the ability to emulate the precise delivery of oxygen by red blood cells is an important function that must be taken into consideration.
Successful and efficient gas transport is the first design consideration when developing a blood substitute. In natural blood systems, O.sub.2 and CO.sub.2 are transported by both convection and diffusion processes. Traditionally, analyses of hemoglobin-based oxygen carriers (HBOCs) have been done at equilibrium, thereby relying on the specific OEC. Further, these analyses have shed light on how HBOC effect vasoactivity in arterioles. The transfusion of HBOC into animal models have produced complex results but the dynamic properties of the cardiovascular system has made the analysis of gas transport properties difficult to obtain. Accordingly, a need remains for a method to analyze oxygen delivery by hemoglobin-based blood substitutes which simulates the physiological properties of the cardiovascular system while being completely removed from that system.